Comparative genetic analysis of pathogenic and attenuated strains of Junín virus

Junín virus (JUNV) is a mammarenavirus that causes Argentine hemorrhagic fever (AHF). Mammarenaviruses are RNA viruses with an ambisense, bi-segmented genome containing four genes encoding the glycoproteins (GPC), the nucleoprotein (NP), the RNA polymerase (L) and the matrix protein (Z). Several JUNV strains with different pathogenicity have already been fully sequenced. We performed a comprehensive and comparative analysis of their genetic differences and phylogeny, focusing on the synonymous codon usage patterns of the JUNV proteins. We found a nucleotide identity of > 95% between strains, with significant differences between all genes for GC% and Z and L genes for GC3%. Analysis of relative synonymous codon usage showed that codons AGA and AGG of the amino acid arginine were overrepresented, while CGC, CGA and CGG of arginine, GCG of alanine, ACG of threonine, CCG of proline and TCG of serine were underrepresented in the GPC, NP and L genes. A weak codon usage bias was observed, with GPC having a significantly higher effective number of codons. Moreover, selection could explain at least 83% of the observed bias. Analysis of the codon adaptation index revealed a better adaptation for B cells and kidney and a lower one for endothelial cells. We also observed a possible reassortment event between the MC2 and Romero strains. This work provides a new perspective on the genetic diversity of JUNV strains, which may contribute to the development of new approaches for future research into the evolutionary model, origin and host adaptation of JUNV causing AHF.